Evaluation of perturbed iron-homeostasis in a prospective cohort of patients with COVID-19

Joe N Frost, Fergus Hamilton*, David Arnold, Karen T Elvers, Akshay Shah, Andrew E Armitage, Alice Milne, Jorgen McKernon, Marie Attwood, Yi-Ling Chen, Luzheng Xue, Jonathan Youngs, Nicholas M Provine, Tihana Bicanic, Paul Klenerman, Hal Drakesmith, Peter Ghazal

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

4 Citations (Scopus)
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Background: Marked reductions in serum iron concentrations are commonly induced during the acute phase of infection. This phenomenon, termed hypoferremia of inflammation, leads to inflammatory anemia, but could also have broader pathophysiological implications. In patients with coronavirus disease 2019 (COVID-19), hypoferremia is associated with disease severity and poorer outcomes, although there are few reported cohorts. Methods: In this study, we leverage a well characterised prospective cohort of hospitalised COVID-19 patients and perform a set of analyses focussing on iron and related biomarkers and both acute severity of COVID-19 and longer-term symptomatology. Results: We observed no associations between acute serum iron and long-term outcomes (including fatigue, breathlessness or quality of life); however, lower haemoglobin was associated with poorer quality of life. We also quantified iron homeostasis associated parameters, demonstrating that among 50 circulating mediators of inflammation IL-6 concentrations were strongly associated with serum iron, consistent with its central role in inflammatory control of iron homeostasis. Surprisingly, we observed no association between serum hepcidin and serum iron concentrations. We also observed elevated erythroferrone concentrations in COVID-19 patients with anaemia of inflammation. Conclusions: These results enhance our understanding of the regulation and pathophysiological consequences of disturbed iron homeostasis during SARS-CoV-2 infection.

Original languageEnglish
Article number173
JournalWellcome Open Research
Early online date21 Jun 2022
Publication statusE-pub ahead of print - 21 Jun 2022

Bibliographical note

Funding Information:
We thank Reza Morovat and Katherine Wray for technical assistance with sample processing.

Publisher Copyright:
© 2022 Frost JN et al.


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